Birth weight, gestational age and intrauterine growth (IUG) are important birth outcomes that significantly contribute to future health. Adverse outcomes including low birth weight (LBW), preterm birth and IUG restriction (IUGR) increase substantially the risks of mortality and disability. About 28% of the 4 million neonatal deaths that occur each year worldwide are related to preterm birth, and about 80% occur among LBW infants. LBW and preterm birth are common outcomes and have been on the rise in the past two decades- 16% of babies worldwide are born at LBW. The etiology of these outcomes remains largely unknown but several environmental, behavioral and genetic risks are thought to be involved through both independent and interactive roles. Reliable studies of birth outcomes in South America have been relatively scarce and most previous studies have relied on limited case-control samples as well as fairly simple statistical techniques that are highly vulnerable to bias. This study aims at obtaining reliable estimates of the rates of adverse birth outcomes and identifying health, demographic, behavioral and socioeconomic risk factors that contribute to these outcomes through independent or interactive effects in unique and large birth samples of non-malformed infants from 8 South American countries (more than 100,000 births) recruited through the Latin American Collaborative Study of Congenital Anomalies (ECLAMC). These samples were recruited using the same sampling and data collection strategy in about 90 hospitals that attend about 180,000 births annually and are well representative of large and understudied South American populations. Data is available on maternal health, fertility and behavioral risks as well as on socioeconomic and demographic factors that may play an important role in these outcomes. A health economics model for health production and advanced multivariate techniques will be used to study the contribution of all potentially relevant inputs and characteristics. The study has important implications by providing a reliable assessment of the burden of adverse birth outcomes in several South America populations, identifying risk factors that can be targeted by health policies and interventions to improve birth outcomes and allowing international comparisons of the effects and roles of various risk factors which further help to identify prevention strategies not only in the studied countries but also in other countries including the US. An example would be comparing the effects of infant and maternal ancestry in these highly admixed populations to those in the US where LBW and preterm rates are found to vary significantly by race. The study also provides a key preliminary step to larger studies of interactive effects between relevant risk factors and genetic variants that may also be involved in these outcomes and to clinical trials that study the effectiveness of selected interventions to improve birth outcomes. PUBLIC HEALTH RELEVANCE: This project aims at identifying determinants of adverse birth outcomes including low birth weight, preterm birth and intrauterine growth restriction in several understudied South American populations. Study results are highly relevant for identifying prevention strategies not only for the included countries but also for others including the United States.